The project is proposed to investigate the biomolecular differences between the subpopulations of T-cells. This will include the subcellular, biochemical evaluation of antigen-specific and non-specific helper T-cells and antigen-specific and non-specific suppressor T-cells. The major biochemical characteristics to be assessed are: 1) the intracellular levels of glutathione (GSH), 2) the ability of the cells to regenerate GSH, 3) the thiol-containing components of the membrane, and 4) the alteration of cellular thiols by permeant and impermeant reducing agents, oxidizing agents, and thiol blockers. Suppressor T-cells are known to be more radiosensitive than helper T-cells (of which antigen-specific helpers are more radiosensitive than non-specific helpers), but the biochemical basis for this greater sensitivity is unknown. These studies will attempt to evaluate the possibility that the differential radiosensitivities (and the cell's longevity) can be correlated with the cell's thiol chemistry. Furthermore, the biochemical basis of macrophage regulation of T-cell activation will be assessed, especially in terms of oxidants and anti-oxidants. The hypothesis that helper macrophages aid in the maintenance of the T-cell's surface thiols and suppressor macrophages reduce the T-cell's surface thiol will be tested. The ability of T-cell subsets to be activated and provide an effector activity will be analyzed in terms of their membrane thiols, intracellular GSH, and release of thiol-reactive constituents. T-cell reactivities can be inhibited by conversion of membrane thiols to disulfides; therefore, thiol-containing membrane complexes will be isolated and analyzed. Surface thiols also will be quantitated with the T-cell subsets in various phases of their activation. A newly synthesized thiol-reactive probe will be utilized for the quantitation, as well as qualitative investigation, of regulatory effects of surface thiols. In addition, the above will be examined in normal (CBA/J), young (1-6 months) mice, as well as in older mice (1-2 years), NZB/NZW mice, and MRL mice.